Objectives: Traditional supine myocardial perfusion imaging (MPI) is commonly associated with artifacts of the anterior wall, apex and inferior wall. The goal of this study is to evaluate the role of ...combined supine (SU) SPECT/CT and prone (PR) SPECT MPI and the effectiveness of CT attenuation correction (CTAC). Methods: A total of 258 patients who underwent same day SU rest/stress SPECT/CT and PR post stress SPECT MPI were assessed for perfusion defects. Images were scored for patient motion, size, intensity and type of perfusion defect, artifacts attenuation (breast, diaphragm, and body habitus), reconstruction (apical thinning) and the effect of CTAC and prone. With respect to distribution, for this part of the study, only defects in the anterior, apex and inferior segments were analyzed. Results: The full protocol of SU SPECT/CT and PR SPECT MPI was successfully completed by 88% of patients. In the (SU) SPECT/CT group 98% of studies had subtle sinogram motion defects; motion correction software was only applied to 38% of studies. PR SPECT MPI allowed for a 25 to 50% improvement in detector tracking. The observed defect score for SU SPECT/CT MPI was 70%, 76% of these defects were related to artifacts. Diaphragmatic attenuation artifact was identified most frequently at 42%. The most observed perfusion defects occurred in the apical segment with extension into the anterior and/or inferior walls. Specifically apical defects accounted for 20% of all SU SPECT/CT MPI defects. Complementary PR SPECT MPI normalized 93% of these defects. PR SPECT MPI also scored better than CTAC for correcting SU artifacts. Attenuation correction was observed to over enhance 60%, partially normalize 16% and only fully normalize 24%. A similar trend was observed in the other analyzed segments. The attached image series is a representation of these observations. Conclusion: SU SPECT/CT is associated with a dramatic rate of defects related to artifacts. Defects associated with attenuation artifacts were drastically reduced with PR SPECT MPI protocol. For defects related to breast attenuation, the prone positioning allows the heart to be closer to the detectors and breast tissue to be compressed anteriorly (ref.1). Apical thinning is a product of supine imaging as they mostly normalize on prone acquisition (ref.2). Furthermore supine defects consistently corrected on prone imaging without the use of CT exposures.